News

Rafal Wieczorek, Mark Dörr and Pierre-Alain Monnard from the MATCHIT Consortium have published a paper on the formation of phosphodiester bonds catalyzed by dipeptides in water/ice eutectic phases. The article is highlighted on the cover of ChemBioChem.

A new method of connecting certain oil molecules could pave the way for intelligent drugs that only target diseased cells. These results from the PNAS-paper has now spred to the science news page Science Nordic.

MATCHIT - Executive Summary

A biological subcellular matrix functions through an intricately coordinated material transportation, information processing and material production system. We seek to mimic these fundamental properties utilizing a hybrid biochemical and information technological system. We introduce an integrated programmable information- and production chemistry by having DNA addressable chemical containers (chemtainers) interfacing traditional electronic computers via microelectromechanical systems (MEMS) with regulatory feedback loops. DNA tags anchored in the chemtainers make them addressable with respect to each other through complementary DNA interaction as well as addressable within a MEMS microfluidics matrix through DNA tags anchored in the micro fluidics channels.

The different types of chemtainers employed are: DNA nano-cages, vesicles (lipid and fatty acid), oil-in-water emulsion droplets and water droplets in ionic liquids. The micro fluidic MEMS matrix with immobilized single stranded DNA represents the interface between the chemtainers and the electronic computers by controlling the attachment of DNA-coated chemtainers.

The abovementioned chemtainers vary significantly in terms of scale and functionality. At the nanoscale, DNA single strands are both the building blocks of the containers and the instance to functionalize them. These DNA cages can open and close controlled by external signals and when closing encapsulate macromolecules as cargo. For the microscale containers, DNA is not used as building material but to address the surface of the chemtainers. These microscopic chemtainers act as either hydrophilic or hydrophobic reaction vessels, which can themselves determine their next processing steps. DNA labeling and addressing of the larger water droplets is also possible. DNA-directed fusion of chemtainers will replace fusion events already shown to be triggered by electrostatic interactions between artificial vesicles. Fission and fusion of chemtainers are formally Membrane computing operations.

A key point for all these technologies is the use of DNA addresses to coordinate the specific assembly of chemtainers in space and time. As an example, we have developed a modular DNA addressing system for supramolecular chemtainers. DNA single strands are incorporated into the surface both of artificial vesicles and of oil-in-water emulsion droplets . In this way we can program the assembly of chemtainers using local base paring rules. Both the sequence and length of the DNA addresses can be modified to ensure both specificity and robust hybridization against denaturing thermal effects. The same methodology directing the assembly of chemtainers is applied to immobilize them to a solid support. Conditions that disfavor the DNA base pairing (i.e. increase of temperature, decrease in salt concentration, addition of competitive DNA) is used to reverse the assembly process of chemtainers. In addition, we have demonstrated that the DNA addresses can be detached from the surface and replaced by new addresses. This allows for altered programmed assembly and a recyclability of our system. Dissipative Particle Dynamics (DPD) simulations are used e.g. to simulate oil-droplets tagged with DNA molecules, using a novel dynamic bonding DNA model.

Using DNA addresses a common language of the diverse types of chemtainers combined with chemical reactions controlled by programmable fusion of chemtainers opens up for a new kind of computing. This computing allows parallel chemical and internal material production programming in a multilevel architecture. Through autonomous DNA address modification (utilizing the usual DNA computing operation) and resolution at the container-container, container-surface, and container-molecule levels, the architecture provides a concrete embedded application for integrated information processing, computing and material production. Self-organizing container addressing can allow micro- and nanoscale processing of any collection of chemicals that can be packaged in the containers. We are developing a calculus that expands, but closely follows the line of brane calculi, for expressing nested addressable membrane systems. The extension of the brane calculus is necessary to accommodate the electronic feedback between the chemtainers and the monitoring-actuating MEMS matrix as well as the spatial addressing. The calculus can both be used for modeling chemtainers, chemtainer addressing and -interactions, as well as ultimately programming the microfluidic device. Elements of the calculus are (possibly nested) chemtainer systems, their cargo, and address tags. Operations of the calculus include chemtainer attachment, fusion, and cargo separation.

By exploiting the latest advances in electronic and biomaterial systems, in MATCHIT we aim to create a hybrid machine/chemistry system for next generation artificial life technologies, ChemBio-ICT. Our approach constitutes a hybrid bottom up construction of life-like and living systems.